Quantitative proteomics reveals systematic dysregulations of liver protein metabolism in sucralose-treated mice

Sucralose, one kind of "sugar-free" artificial sweeteners, is widely used as food and drinks additives. It is generally considered that sucralose is safe because majority of ingested sucralose is not metabolized and absorbed by human body. However, increasing evidence shows the negative effects of artificial sweeteners in perturbations of gut microbiota which plays an important role in a variety of processes related to host health such as immune system development. Specifically, sucralose uptake can alter the homeostasis of mouse gut microbiota, resulting in the significant changes of gut bacterial genera diversity, metabolic patterns, and fecal metabolite profiles as well as inducing host liver inflammation. Therefore, there is a need to study liver proteome changes which may be potentially affected by sucralose-induced dysbiosis. In this study, isobaric labeling-based quantitative proteomics was performed to reveal the liver functional proteome changes in male C57BL/6J mice with sucralose administration in drinking water for six-month period. The labeled tryptic peptides were off-line fractionated before LC-MS/MS analysis to improve proteome coverage detected. SIGNIFICANCE: We demonstrated the first quantitative proteomics for mice liver proteome to evaluate the effect of sucralose consumption. In total, >5700 protein groups were identified from 18 mouse liver tissues (9 from control group; 9 from sucralose-treated group), and 4327 protein groups were quantified in all samples without any missing values. Among them, 113 protein groups were identified with statistical significance (q value <0.05) as differentially expressed proteins. Bioinformatics analysis revealed the systematic dysregulations of protein metabolism after sucralose treatment. Importantly, our findings proposed that enhanced inflammation may be triggered by ribosomal inactivation in sucralose treated mice liver.